ArticleInternational journal of molecular sciences2026
Sexual Dimorphism in the Initial Apoptotic Switch During MASH Progression in Mice.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
MASH is a progressive liver disease closely associated with cellular senescence, which is present in more than 80% of hepatocytes in patients who develop hepatocellular carcinoma (HCC). Although MASH affects both sexes, the incidence of MASH-related HCC is two to four times higher in males. Our group has previously described two apoptotic switches during MASH progression and HCC development, implicating the ATP1A1 signalosome in the late switch. Here, we investigated the role of ATP1A1 and sex-specific differences in the early apoptotic switch during preclinical MASH progression. Male and female C57BL/6J mice (7 weeks old) were fed normal mouse chow (NMC) or a high-fat diet (HFD) for 12, 24, or 48 weeks (n = 5/sex/group). Total body weight (TBW) and body composition were assessed by serial measurement and echo-MRI. Plasma was analyzed by non-targeted metabolomics and glutathione profiling using LC-MS/MS. NAFLD activity scores (NAS), hepatic senescence, and apoptosis were quantified in liver tissue. Statistical analyses were performed using GraphPad Prism and R. Males gained greater TBW and lean and fat mass than females (
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